MassGeneral Hospital for Children News

Researchers in the Center for Regenerative Medicine at Massachusetts General Hospital and the Harvard Stem Cell Institute have taken a critical step toward a treatment for Cystic fibrosis and other fatal lung diseases.

Mass General Researchers Take Major Step Toward a Treatment for Cystic Fibrosis

05/Apr/2012

Researchers in the Center for Regenerative Medicine at Massachusetts General Hospital have overcome a major hurdle in the pursuit of a treatment for Cystic fibrosis (CF) and other fatal lung diseases. Dr. Jayaraj Rajagopal, a pulmonologist at MassGeneral Hospital for Children, and colleagues managed to create human lung tissue using skin cells from CF patients.

Mice, the most commonly used model in biomedical research, don’t get lung diseases the way humans do. Lung diseases such as cystic fibrosis, asthma, and lung cancer are a very human phenomenon and difficult to reproduce in an animal model. But human airway tissue is in limited supply. For years, researchers have been forced to continue using a mouse model or screen drugs using a very limited supply of existing human tissue.

“Since we knew the signals that made the mouse lung, we were able to recapitulate those with mouse stem cells. Then we transferred what we learned from mouse stem cells to human stem cells and we were essentially able to make airway tissue from patient skin,” Rajagopal, the senior author on the study, said.

The research, published April 5 in the journal Cell Stem Cell, details how Rajagopal’s team used skin cells from patients with CF to create induced pluripotent stem cells (iPS) and then used these stem cells to create human disease-specific functioning epithelium – the tissue that lines the airways and is the main target of the CF gene.

The paper, co-authored by post-doctoral fellow Hongmei Mou, was a collaborative effort. Rajagopal and Mou partnered with the Harvard Stem Cell Institute and worked with Darrell Kotton’s lab at Boston University, which was able to convert mouse cells into lung tissue.

With the ability to create their own supply of CF airway tissue, Rajagopal said his team now has enough tissue to share with other researchers and to begin manipulating them to screen for possible treatments.

“Now that we can genetically manipulate these cells, we think that we can come up with better and better screens,” he said. “There are simple screens that just look for the perfect drug that fixes everything in one step, but life might be a lot more complicated and you might need two drugs at the same time. Previously, because of the amount of tissue that was available, those kinds of combinatory screens would have been impossible. Plus, they were doing those kinds of screens on the wrong cells, so the drugs that you were finding were likely not to be the right ones to work in the proper cells.”

The research gives added hope to CF patients with the delta-508 mutation, the gene responsible for about 70 percent of all cases of CF and 90 percent of the cases in the U.S. Rajagopal’s team was also able to grow tissue containing the G551D mutation, a gene affecting approximately two percent of CF cases and the one cause of CF for which there is now a drug treatment.

The implications go beyond CF. “We’re hoping to apply the principle to all diseases that affect the airway, including very important and common diseases like lung cancer, like asthma, like bronchitis and a host of other diseases,” Rajagopal said. “So in many ways I think the most important thing about this research is it’s a new platform for dissecting human lung disease.”